Breast cancer mortality is the second leading cause of cancer death in women. In spite of improvements in stage and advances in treatment, mortality from breast cancer continues to be substantial and there exists a paucity of insights regarding factors that influence disease progression and mortality. In particular, little is known about how patient and tumor characteristics relate to mortality in middle- and older aged women. We propose to conduct a population-based molecular-epidemiologic cohort study of factors that predict mortality in women diagnosed with invasive breast cancer at ages 45 through 79. The overall goal of the study is to evaluate patient and tumor characteristics for their relationship with the risk of breast cancer mortality. The proposed cohort consists of 2337 women diagnosed with a first invasive breast cancer at 45-79 years of age during the period 1993-1999, all of whom previously completed an extensive interview regarding exposures prior to diagnosis and will now be followed for mortality. Telephone interviews and medical record reviews will be used to collect information on exposures after diagnosis, disease recurrences, and treatment details. Tumor characteristics and markers will be assessed in relation to both mortality and patient factors as a basis for understanding determinants of prognosis. The aims of this study are: (1) to determine if patient characteristics and exposures (before and after diagnosis), including some which are potentially modifiable, are related to the risk of dying from breast cancer, (2) to determine if patient characteristics and exposures prior to diagnosis are associated with histopathologic features and tumor markers, (3) to assess the relationship of histopathologic factors and tumor markers, including both well characterized prognostic markers and less well-characterized cell cycle proteins, with the risk of dying from breast cancer, (4) to build tissue microarrays that will allow rapid assessment of future markers as they are identified, (5) to build a comprehensive resource for future ancillary studies. The investigation of tumor and patient characteristics in relation to mortality could provide etiologic and clinical insights regarding determinants of prognosis and help to generate clues regarding the biology of breast cancer progression.